Gene therapy is to correct or compensate for defects of genes, shut down or inhibit the expression of abnormal genes by introducing an exogenous gene DNA or RNA fragment to target cells or tissues, so as to achieve the purpose of treating diseases. As a new therapeutic means, gene therapy can treat various diseases, including cancer, genetic disorders, infectious diseases, cardiovascular diseases and autoimmune diseases. Wherein, cancer gene therapy is the main application field of gene therapy. During the development of gene therapy for decades, there are nearly 2000 cases of clinical trials of gene-transfected gene therapy launched in all over the world. In 1990, Culver et al. from National Institutes of Health first applied gene therapy to clinical trials, and they by a gene therapy method treated adenosine deaminase (ADA) deficiency and succeeded. In 2000, French successfully used the technology of gene therapy to cure Combined Immunodeficiency Syndrome (X-SCID), thereby confirming the effectiveness of gene therapy strategy. However, if the gene therapy would like to get further development, there are the following three problems we must overcome: firstly, there must be a target gene for treatment and a cell accepting the target gene; secondly, to realize the regulatability of gene expression; thirdly, obtain targeted gene vector system with high efficiency and low toxicity. Among them, the targeted gene vector system with high efficiency is one of the bottlenecks restricting the development of gene therapy.
Cationic liposomes have cell-like structures and characteristics of biofilm, they can be degraded in vivo and can protect biological activity of gene fragments carried by them, so they are non-viral gene transfection vectors with a clinical application potentiality. Such structures of liposomes make it possible to enclose drug powder or compress genes to form complexes and deliver them to diseased tissues or cells, after entering into the human body, they are mainly phagocytosed by a reticuloendothelial system to activate the body's own immune function and to change in-vivo distribution of the encapsulated drug, in order that the drug is mainly accumulated in the liver, spleen, lung and bone marrow and other tissues and organs, thereby improving the therapeutic index of the drug, reducing the therapeutic dose of the drug and reducing the toxicity of the drug. Since 1987 Felgner et al. first using N-[1-(2,3-dioleyloxy) propyl]-N,N,N-trimethyl ammonium chloride (DOTMA) successfully transfected cells such as COS-7 etc., liposome has been developed to be the most widely used gene delivery methods in addition to retroviral vectors, and more particularly in the treatment of diseases such as tumors and cystic fibrosis, etc. However, because it still has some limitations, for example, the high cell toxicity, organ targeting is not obvious, the gene transfer mechanism is unclear, and these limit its wider application. Therefore, people have been working on various constructions and chemical modifications of cationic liposomes, seeking to find a gene therapy vector with high efficiency and low toxicity.
For nearly 30 years development of liposomes, from widely used cationic lipid with quaternary ammonium salt head, guanidino head to cationic lipid with polyamine head, there has been formed relatively complete liposome vector systems, but these vector systems still have many problems, for example, the transportation efficiency of mediated gene needs to be improved; lack of directional recognition for target tissues; after cationic liposomes/DNA complexes entering into a cell, nucleic acid is bound inside the endosome and can hardly be released, which is unfavorable for the expression in cytoplasm or nucleus, thereby making it impossible to achieve therapeutic purposes. A Chinese invention patent CN103553970A, Feb. 5, 2014, discloses preparation of urethane-type cationic lipid and application of the same in drugs or gene transportation, although this vector has an efficient gene transportation capability, it has certain cytotoxicity due to its structure of a quaternary ammonium salt head, so it is limited in the aspect of gene transportation in vivo.